Ignite Creation Date:
2024-05-06 @ 10:05 AM
Last Modification Date:
2024-10-26 @ 12:24 PM
Study NCT ID:
NCT03163394
Status:
TERMINATED
Last Update Posted:
2020-02-27
First Post:
2017-05-18
Brief Title:
HD5 Levels in Catheter Versus Bag Urine Specimens in Young Children for the Diagnosis of UTI
Sponsor:
Le Bonheur Childrens Hospital
Organization:
Le Bonheur Childrens Hospital
Study Overview
Official Title:
HD5 Levels in Catheter Versus Bag Urine Specimens in Young Children for the Diagnosis of UTI
Status:
TERMINATED
Status Verified Date:
2020-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Did not enroll enough patients for study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Urinary tract infections UTIs are a common cause of bacteremia and serious bacterial infections in young children 2-24 months of age Because these children are usually unable to say what symptoms they are experiencing UTIs are diagnosed through testing Current testing of urine samples require a catheter or suprapubic aspiration performed for urine collection for infections markers to be reliable Bag specimens often have varying results that can be poor in sensitivity and specificity depending on what component of the urine test one is looking at Catheter and aspiration testing can be anxiety-provoking to parents be painful for patients and even introduce bacteria into the bladder An antimicrobial peptide called alpha human defensin-5 HD5 is produced by the uroepithelium in response to infection HD5 has been studied in the urine and does increase in actual UTIs This study will look at children 1 to 24 months of age and again study levels of HD5 in culture positive UTIs versus urine negative for UTI This study will also determine if collection method alters HD5 levels We will measure HD5 levels in the urine from a bag specimen and a catheter specimen in the same patient
Our primary objective is to determine the sensitivity and specificity of HD5 measured in urine collected by bag and catheter in the same patient for the diagnosis of UTI in children between the age 1 to 24 months presenting with febrile illness and suspected UTI
Our primary objective is to determine the sensitivity and specificity of HD5 measured in urine collected by bag and catheter in the same patient for the diagnosis of UTI in children between the age 1 to 24 months presenting with febrile illness and suspected UTI
Detailed Description:
Pediatric urinary tract infections UTIs are a common diagnosis and account for greater than 500000 emergency department ED visits each year in the US Although prevalence varies by age gender ethnicity and circumcision status the overall prevalence is cited between 5 to 138 UTIs also account for a large number of pediatric hospital admissions with up to 50000 children admitted per year 40 of which occurring in children under the age of 1 year In children under the age of two diagnosis of UTI is difficult as patients are unable to verbalize complaints and often present with only fever or other nonspecific symptoms such as vomiting UTIs are the leading cause of occult bacteremia and serious bacterial infection in the 2-24 month age range
A definitive diagnosis of UTI is made when a patient has pyuria andor bacteriuria with a positive urine culture For non-toilet trained children who have urine collected by either suprapubic aspiration SPA or bladder catheterization a urine culture is considered positive if a single uropathogenic organism of at least 50000 colony forming units CFU per mL is recovered Identification of a uropathogen by culture can take up to 48 hours to be completed which delays treatment and risks progression of infection if antibiotics are not given empirically Commonly clinicians use urine microscopy and dipstick for quick diagnosis to enable early empiric treatment of UTIs However the components of the urinalysis are limited in sensitivity and specificity even for specimens of high quality such as those obtained by catheterization or suprapubic tap The main components of urine dipstick testing are leukocyte esterase LE and nitrite levels in urine The LE test has a sensitivity of 94 when combined with clinical suspicion for UTI but a specificity of only 83 False positives for UTI occur when LE is positive in the child who has pyuria for other reasons besides infection for example in urethritis or Kawasaki disease False negatives can occur in young children because the pattern of more frequent urination allows less time to mount an adequate inflammatory response to bacteria Nitrites have a low sensitivity in young children 53 due to frequent voiding not allowing sufficient time up to 4 hours for production of nitrites by bladder-dwelling bacteria however specificity is high 98 making this a good test to rule in UTI Sensitivity and specificity of urine microscopy for WBCs and bacteria are worse than for LE with pyuria 5 or more WBChigh power field on a spun sample or 10 WBChpf on an un-spun sample having a sensitivity and specificity of 73 and 81 respectively Presence of bacteria on microscopy has a sensitivity and specificity of 81 and 83 respectively The resulting over- and under-treatment for false positive and negative urinalyses leads to increased costs antibiotic resistance and unnecessary adverse events from antibiotics The inaccuracy of the traditional urinalysis on bagged urine samples is much greater than for catheter specimens These specimens suffer from false positives results for leukocyte esterase and cultures at rates up to 75-88 because of contamination by urogenital flora and white blood cells present on the perineum
As a result of the poor performance characteristics of routine urinalyses on bag specimens a sample obtained by catheterization in children who are not yet toilet-trained is required even for UTI screening This is invasive and painful for the child causes anxiety for the family leads to urethral trauma and can even introduce bacteria into the urinary system Recent research describes a new two-step technique of obtaining urine samples of screening for UTI on these young patients First a bagged urine sample is taken and if suspicious for UTI by urinalysis the patient then is catheterized for culture One study showed that this technique decreased the number of catheterizations by 33 however given the low specificity of the urinalyses on bag specimens there is still substantial room for reductions in unnecessary bladder catheterizations
New urinary biomarkers hold promise to improve screening accuracy for UTIs Watson et al investigated antimicrobial peptides AMPs as urinary biomarkers of UTIs in children One specific AMP derived from the epithelium is human alpha-defensin 5 HD5 This AMP is produced by intestinal Paneth cells the female genital tract and the uroepithelium HD5 was found to have mean concentration significantly higher in the urine from culture-positive compared to culture-negative specimens When used in combination with LE HD5 increased the specificity of the LE-only test by 6 without decreasing the sensitivity 97 for LE trace This study determined the optimal cut-off value of 174 pgmg creatinine to declare sample positive Because HD5 is not derived from white blood cells its presence is not affected by the presence or absence of WBCs in the urine to accurately identify urinary inflammation While the authors of this study examined results from both clean-catch and catheterized specimens they did not analyze samples collected by both techniques from the same patient
Identification and validation of biomarkers with improved performance characteristics could reduce over-treatment of UTIs validating such biomarkers on bag urine specimens has the further benefit of reducing the need for catheterization to provide urine to screen for UTI in a relatively unselected population of young children who have fever without a focus We propose to compare the use of HD5 in bag versus catheter urine samples on children 1 to 24 months of age to determine if the biomarker has similarly high sensitivity and specificity to the original study in both specimen types Eliminating the need for urine culture would also save on costs for children whose rapid testing does not suggest UTI Reducing the number of catheterizations performed on young children will decrease the number of painful procedures prevent introduction of bacteria in the urinary tract and decrease parental anxiety
A definitive diagnosis of UTI is made when a patient has pyuria andor bacteriuria with a positive urine culture For non-toilet trained children who have urine collected by either suprapubic aspiration SPA or bladder catheterization a urine culture is considered positive if a single uropathogenic organism of at least 50000 colony forming units CFU per mL is recovered Identification of a uropathogen by culture can take up to 48 hours to be completed which delays treatment and risks progression of infection if antibiotics are not given empirically Commonly clinicians use urine microscopy and dipstick for quick diagnosis to enable early empiric treatment of UTIs However the components of the urinalysis are limited in sensitivity and specificity even for specimens of high quality such as those obtained by catheterization or suprapubic tap The main components of urine dipstick testing are leukocyte esterase LE and nitrite levels in urine The LE test has a sensitivity of 94 when combined with clinical suspicion for UTI but a specificity of only 83 False positives for UTI occur when LE is positive in the child who has pyuria for other reasons besides infection for example in urethritis or Kawasaki disease False negatives can occur in young children because the pattern of more frequent urination allows less time to mount an adequate inflammatory response to bacteria Nitrites have a low sensitivity in young children 53 due to frequent voiding not allowing sufficient time up to 4 hours for production of nitrites by bladder-dwelling bacteria however specificity is high 98 making this a good test to rule in UTI Sensitivity and specificity of urine microscopy for WBCs and bacteria are worse than for LE with pyuria 5 or more WBChigh power field on a spun sample or 10 WBChpf on an un-spun sample having a sensitivity and specificity of 73 and 81 respectively Presence of bacteria on microscopy has a sensitivity and specificity of 81 and 83 respectively The resulting over- and under-treatment for false positive and negative urinalyses leads to increased costs antibiotic resistance and unnecessary adverse events from antibiotics The inaccuracy of the traditional urinalysis on bagged urine samples is much greater than for catheter specimens These specimens suffer from false positives results for leukocyte esterase and cultures at rates up to 75-88 because of contamination by urogenital flora and white blood cells present on the perineum
As a result of the poor performance characteristics of routine urinalyses on bag specimens a sample obtained by catheterization in children who are not yet toilet-trained is required even for UTI screening This is invasive and painful for the child causes anxiety for the family leads to urethral trauma and can even introduce bacteria into the urinary system Recent research describes a new two-step technique of obtaining urine samples of screening for UTI on these young patients First a bagged urine sample is taken and if suspicious for UTI by urinalysis the patient then is catheterized for culture One study showed that this technique decreased the number of catheterizations by 33 however given the low specificity of the urinalyses on bag specimens there is still substantial room for reductions in unnecessary bladder catheterizations
New urinary biomarkers hold promise to improve screening accuracy for UTIs Watson et al investigated antimicrobial peptides AMPs as urinary biomarkers of UTIs in children One specific AMP derived from the epithelium is human alpha-defensin 5 HD5 This AMP is produced by intestinal Paneth cells the female genital tract and the uroepithelium HD5 was found to have mean concentration significantly higher in the urine from culture-positive compared to culture-negative specimens When used in combination with LE HD5 increased the specificity of the LE-only test by 6 without decreasing the sensitivity 97 for LE trace This study determined the optimal cut-off value of 174 pgmg creatinine to declare sample positive Because HD5 is not derived from white blood cells its presence is not affected by the presence or absence of WBCs in the urine to accurately identify urinary inflammation While the authors of this study examined results from both clean-catch and catheterized specimens they did not analyze samples collected by both techniques from the same patient
Identification and validation of biomarkers with improved performance characteristics could reduce over-treatment of UTIs validating such biomarkers on bag urine specimens has the further benefit of reducing the need for catheterization to provide urine to screen for UTI in a relatively unselected population of young children who have fever without a focus We propose to compare the use of HD5 in bag versus catheter urine samples on children 1 to 24 months of age to determine if the biomarker has similarly high sensitivity and specificity to the original study in both specimen types Eliminating the need for urine culture would also save on costs for children whose rapid testing does not suggest UTI Reducing the number of catheterizations performed on young children will decrease the number of painful procedures prevent introduction of bacteria in the urinary tract and decrease parental anxiety
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None